Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A
Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A
复制标题
甲型流感神经氨酸酶强效抑制剂含吡啶基奥司他韦衍生物的设计、合成及生物学评价
DOI：
10.1016/j.ejmech.2019.111841
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发表时间：
2020-01-01
影响因子：
6.7
通讯作者：
Tian, Yongshou
中科院分区：
文献类型：
--
作者：
Wang, Kuanglei;Lei, Zaigiang;Tian, Yongshou
Influenza A neuraminidase plays an indispensable role in the process of replication and transmission of influenza, so the neuraminidase inhibition can prevent the reproduction of the viruses therefore achieve the effect of treatment of influenza. However, drug resistance of neuraminidase inhibitors such as oseltamivir highlights the need to develop novel structural neuraminidase inhibitors. Here we explored a series of oseltamivir derivatives bearing pyridyl group. Among them, compound 23b exhibiting potent inhibitory activity against neuraminidase from H5N1 subtype was comparable to oseltamivir carboxylate. Cytopathic effect inhibition assay in MDCK cells indicated that compound 23b exerted powerful inhibitions on influenza viruses. And compound 23b were nontoxic to MDCK cells. Meanwhile, compound 23b showed high stability towards rat liver microsomes, human liver microsomes and human plasma. This research enriched the structural type of neuraminidase inhibitors. (C) 2019 Elsevier Masson SAS. All rights reserved.
